Featured Research

from universities, journals, and other organizations

Molecular pathway through which common yeast becomes fungal pathogen determined

Date:

March 16, 2012

Source:

University of Toronto

Summary:

Scientists have found a molecular mechanism that plays a key role in the transition of Candida albicans yeast into disease-causing fungus -- one of the leading causes of hospital-acquired infection. The finding highlights the importance of heat in fungal growth, and provides a new target for drug therapies to counter Candida albicans infection. In an additional study, the researchers identified 224 new genetic interactors for central protein in Candida albicans.

Share This

Scientists at the University of Toronto have found a molecular mechanism that plays a key role in the transition of Candida albicans yeast into disease-causing fungus -- one of the leading causes of hospital-acquired infection. The finding highlights the importance of heat in fungal growth, and provides a new target for drug therapies to counter Candida albicans infection.

Related Articles

Candida albicans is a normally harmless yeast that is present in all humans. It becomes infectious in various genetic and environmental conditions, with temperature as a key determinant. It can produce infections that are mild -- persistent vaginal or gut infections, for example -- or severe, such as systemic, potentially fatal bloodstream infections in patients with AIDS or those who have undergone chemotherapy (or even a simple round of antibiotics).

The molecular workings of Candida albicans were mapped for the first time in 2009 by Professor Leah Cowen of the University of Toronto's Department of Molecular Genetics, whose lab showed that growth of the fungus is tied to the function of a "molecular chaperone" called heat- shock protein 90 (Hsp90). In a study that will appear in the March 20 edition of the journal Current Biology, Prof. Cowen and her colleagues detail a mechanism that controls response to elevated temperature through a protein named Hms1 in conjunction with a cyclin (another type of protein) and its partner protein called a cyclin-dependent kinase.

"This circuitry fundamentally influences how Candida albicans senses temperature, which is crucial for Candida's ability to cause disease," said Prof. Cowen, who holds the Canada Research Chair in Microbial Genomics and Infectious Disease -- a prestigious five-year award for which she was renewed this week.

"We were looking for a transcription factor at the end of a pathway we previously showed was key to the change in shape of the fungus that accompanies elevated temperature or compromise of Hsp90 function, and instead we found an entirely new pathway, with components that haven't been characterized in Candida, so it was very surprising," said Prof. Cowen.

The researchers also showed that deletion of Hms1 inhibits Candida albicans infection, pointing toward a possible clinical therapy. "We observed those weaker disease phenotypes in an insect model system, but the results suggest it may also work in more complicated systems," said Prof. Cowen.

The source of pesky vaginal and gut infections, Candida albicans is a burgeoning problem on implanted medical devices -- it's fatal in roughly one-third of device-associated infections -- and is the fourth-leading cause of hospital-acquired infection. The number of acquired fungal bloodstream infections has increased by more than 200% over the last twenty years, owing in part to growing numbers of AIDS and cancer survivors whose treatments have compromised their immune function.

On finding that the Hms1 pathway affects the growth and development of Candida albicans, and knowing of other key regulators through which Hsp90 operates and suspecting many more exist, Prof. Cowen and her lab examined other pathways and proteins that interact with Hsp90 in another study.

In collaboration with Professor Gary Bader at U of T's Donnelly Centre for Cellular and Biomolecular Research, Prof. Cowen's group mapped a much larger portion of the chaperone network with which Hsp90 interacts through a "chemical genomics" approach that had never been applied to Candida albicans. "If we want to have a more global understanding of what Hsp90 is doing during the transition of this fungus between distinct morphological states with different disease causing properties, we need to take global approaches to determine what its interacting with," said Prof. Cowen.

Their results, published online today in the journal PLoS Genetics, showed 226 genetic interactors with Hsp90 in various conditions, such as different temperatures and during exposure to anti-fungal drugs. Of those interactions, 224 were previously unknown. "That's a lot," said Prof. Cowen. "We now have a myriad of new targets through which Hsp90 could be regulating morphogenesis and drug resistance in Candida."

As well, the researchers drew several predictive rules from their study that govern the Hsp90 chaperone network. Some interactors were only important in a small subset of stress conditions, and these are likely to function "downstream" of Hsp90 regulating specialized cellular processes. Other interactors were important in many stress conditions, and so are likely to work "upstream" of Hsp90 regulating its function.

"Hsp90 stabilizes many proteins, but previously nobody could predict what made an Hsp90 client. That we can make such predictions from the chaperone network is pretty cool and unanticipated, so we're further ahead than we expected," said Prof. Cowen.

University of Toronto. "Molecular pathway through which common yeast becomes fungal pathogen determined." ScienceDaily. ScienceDaily, 16 March 2012. <www.sciencedaily.com/releases/2012/03/120316112642.htm>.

University of Toronto. (2012, March 16). Molecular pathway through which common yeast becomes fungal pathogen determined. ScienceDaily. Retrieved March 3, 2015 from www.sciencedaily.com/releases/2012/03/120316112642.htm

University of Toronto. "Molecular pathway through which common yeast becomes fungal pathogen determined." ScienceDaily. www.sciencedaily.com/releases/2012/03/120316112642.htm (accessed March 3, 2015).

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015  Scientists have discovered a new hormone that fights the weight gain caused by a high-fat Western diet and normalizes the metabolism -- effects commonly associated with exercising. When tested in ... full story

Mar. 3, 2015  New assays can detect malaria parasites in human blood at very low levels and might be helpful in the campaign to eradicate malaria, reports a new study. An international team led by Ingrid Felger, ... full story

Mar. 3, 2015  Adults over the age of 30 only catch flu about twice a decade, a new study suggests. So, while it may feel like more, flu-like illness can be caused by many pathogens, making it difficult to assess ... full story

Mar. 3, 2015  No significant change in home habits of smokers have been observed in the aftermath of a ban on smoking in public spaces, researchers report. Greater inspiration to kick the habit likely comes from ... full story

Mar. 3, 2015  Heart function has been associated with the development of dementia and Alzheimer's disease through a new study. Participants with decreased heart function, measured by cardiac index, were two to ... full story

Mar. 3, 2015  Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015  Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015  Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015)  After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015)  Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13
Video provided by AFP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015)  A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Sep. 12, 2013  A research team has found a breakthrough herbal medicine treatment for a common human fungal pathogen that lives in almost 80 percent of people. The team discovered a medicinal herb called Gymnema ... full story

Sep. 2, 2013  Candida albicans is a common fungus found living in, and on, many parts of the human body. Usually this species causes no harm to humans unless it can breach the body’s immune defenses, where can ... full story

July 24, 2012  Researchers have now shown how a common fungus can adjust its physiology to become harmful in a host with compromised immune status. The study is the first to demonstrate that the hospitality of the ... full story

May 1, 2010  A bacterial pathogen can communicate with yeast to block the development of drug-resistant yeast infections, say scientists. The research could be a step towards new strategies to prevent ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.